SELENOF

Summary

SELENOF (selenoprotein F, HGNC:17705) is a protein-coding gene on chromosome 1p22.3, encoding Selenoprotein F (O60613). May be involved in redox reactions associated with the formation of disulfide bonds.

The protein encoded by this gene belongs to the SEP15/selenoprotein M family. The exact function of this protein is not known; however, it has been found to associate with UDP-glucose:glycoprotein glucosyltransferase (UGTR), an endoplasmic reticulum(ER)-resident protein, which is involved in the quality control of protein folding. The association with UGTR retains this protein in the ER, where it may play a role in protein folding. It has also been suggested to have a role in cancer etiology. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 9403 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_004261

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17705
Approved symbol	SELENOF
Name	selenoprotein F
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	SEP15
Ensembl gene	ENSG00000183291
Ensembl biotype	protein_coding
OMIM	606254
Entrez	9403

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000331835, ENST00000370554, ENST00000401030, ENST00000467557, ENST00000469566, ENST00000497861, ENST00000648872

RefSeq mRNA: 2 — MANE Select: NM_004261 NM_004261, NM_203341

CCDS: CCDS76177, CCDS76178

Canonical transcript exons

ENST00000331835 — 5 exons

Exon	Start	End
ENSE00001302264	86862445	86863605
ENSE00001453004	86914028	86914126
ENSE00003572163	86903281	86903448
ENSE00003588929	86880662	86880725
ENSE00003627533	86868053	86868102

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.3863 / max 1529.0259, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13113	80.4663	1825
13114	3.9200	1346

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.15	gold quality
pigmented layer of retina	UBERON:0001782	98.99	gold quality
corpus epididymis	UBERON:0004359	98.95	gold quality
seminal vesicle	UBERON:0000998	98.93	gold quality
monocyte	CL:0000576	98.92	gold quality
stromal cell of endometrium	CL:0002255	98.86	gold quality
mononuclear cell	CL:0000842	98.84	gold quality
leukocyte	CL:0000738	98.82	gold quality
caput epididymis	UBERON:0004358	98.74	gold quality
gall bladder	UBERON:0002110	98.67	gold quality
rectum	UBERON:0001052	98.66	gold quality
epithelium of nasopharynx	UBERON:0001951	98.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.66	gold quality
palpebral conjunctiva	UBERON:0001812	98.63	gold quality
endometrium	UBERON:0001295	98.56	gold quality
left lobe of thyroid gland	UBERON:0001120	98.45	gold quality
germinal epithelium of ovary	UBERON:0001304	98.41	gold quality
thyroid gland	UBERON:0002046	98.41	gold quality
skin of hip	UBERON:0001554	98.40	gold quality
superficial temporal artery	UBERON:0001614	98.38	gold quality
bronchial epithelial cell	CL:0002328	98.37	gold quality
right lobe of thyroid gland	UBERON:0001119	98.35	gold quality
vermiform appendix	UBERON:0001154	98.32	gold quality
tibia	UBERON:0000979	98.31	gold quality
left adrenal gland	UBERON:0001234	98.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.30	gold quality
lymph node	UBERON:0000029	98.25	gold quality
endocervix	UBERON:0000458	98.24	gold quality
synovial joint	UBERON:0002217	98.23	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	46.77
E-MTAB-2983	no	1191.84
E-MTAB-8530	no	900.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting SELENOF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4694-3P	99.79	69.53	2640

Literature-anchored findings (GeneRIF, showing 20)

• Genetic and functional analysis of mammalian Sep15 selenoprotein. (PMID:11898406)
• Studies in mouse show that Sep15 may have redox function. (PMID:12600282)
• SEP15, encoding a 15-kDa selenium-containing protein was shown to be downregulated in approximately 60% of MM cell lines and tumor specimens. A SEP15 polymorphic variant, 1125A, resides in the SECIS recognition element (PMID:15107826)
• It appears that those with the Sep15 1125 AA genotype may benefit most from a higher Se intake, whereas in those with the GG or GA genotype, a higher Se status may increase the risk for lung cancer. (PMID:18239845)
• This study provides evidence that SEP15 genetic variation may influence prostate cancer mortality (PMID:20424130)
• Concerning rs561104, the serum selenium concentration was higher in CC homozygotes (5.65 +/- 1.11 mug/dL) compared with T carriers (4.88 +/- 1.25 mug/dL, P = .044). (PMID:25249019)
• Sep15 in Chang liver cells regulates the pathway that antagonizes RhoA/ROCK/MLC-dependent non-apoptotic bleb formation. (PMID:25529450)
• Results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility of Chang liver cells offering a novel functional link between the cell cycle and cell motility. (PMID:25728752)
• Genotype variation within the 3’-UTR of the SEP 15 gene showed no association with breast cancer risk or clinico-pathological parameters in Caucasian women. (PMID:26264612)
• The allelic and genotypic frequencies did not differ between rapid and nonrapid progressors; however, the presence of the AA genotype of the rs5859 polymorphism was associated with a shorter time of progression to AIDS compared with GG homozygotes (hazard ratio = 3.62, 95% CI = 1.55-8.43, p = 0.003). (PMID:27228552)
• The study suggests the possible importance of SEPP1 rs3877899 and SEP15 rs5859 polymorphisms in susceptibility to breast cancer. (PMID:28598259)
• Results indicate an interaction between selenium status and selenoprotein genotypes that may contribute to the disparity in prostate cancer incidence and outcome experienced by African Americans (PMID:29314169)
• The aim of the study was to investigate the association between rs5859 in Sep15, rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the expression of AP-1 pathway. (PMID:29653292)
• this work has provided experimental data for the molecular mechanism of SELENOF gene regulation, as well as uncovered the involvement of HSF1 in selenotranscriptomic for the first time. (PMID:31109102)
• Association of the selenoprotein 15-kDa (SEP15) polymorphisms with cancer risk: a meta-analysis. (PMID:31665936)
• Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells. (PMID:34769469)
• SELENOF is a new tumor suppressor in breast cancer. (PMID:35082382)
• One-Pot Chemical Protein Synthesis Utilizing Fmoc-Masked Selenazolidine to Address the Redox Functionality of Human Selenoprotein F. (PMID:35112407)
• Role of SELENBP1 and SELENOF in prostate cancer bioenergetics. (PMID:36334799)
• Distinct Roles of SELENOF in Different Human Cancers. (PMID:36979420)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	selenof	ENSDARG00000099664
mus_musculus	Selenof	ENSMUSG00000037072
rattus_norvegicus	Selenof	ENSRNOG00000055257
drosophila_melanogaster	CG7484	FBGN0036745
caenorhabditis_elegans		WBGENE00022297

Paralogs (1): SELENOM (ENSG00000198832)

Protein

Protein identifiers

Selenoprotein F — O60613 (reviewed: O60613)

Alternative names: 15 kDa selenoprotein

All UniProt accessions (5): O60613, A0A0J9YX89, A0A0J9YXM9, A0A3B3IT39, A8MZD0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in redox reactions associated with the formation of disulfide bonds. May contribute to the quality control of protein folding in the endoplasmic reticulum. May regulate protein folding by enhancing the catalytic activity of UGGT1/UGCGL1 and UGGT2/UGCGL2.

Subunit / interactions. Forms a tight complex with UGGT1/UGCGL1. Interacts with UGGT2/UGCGL2. Interacts with RDH11.

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Higher levels in prostate and thyroid gland.

Post-translational modifications. The N-terminus is blocked.

Similarity. Belongs to the selenoprotein M/F family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60613-1	1	yes
O60613-2	2

RefSeq proteins (2): NP_004252, NP_976086 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014912	Sep15_SelM_dom	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR038219	Sep15/SelM_sf	Homologous_superfamily
IPR039992	Sep15_SelM	Family

Pfam: PF08806

UniProt features (6 total): splice variant 2, signal peptide 1, chain 1, non-standard amino acid 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for O60613 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
96	does not affect protein folding and binding to uggt1 or uggt2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GOBP_MALE_GAMETE_GENERATION, SP1_Q2_01, EFC_Q6, PUJANA_CHEK2_PCC_NETWORK, GOBP_PROTEIN_MATURATION, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, MARTINEZ_RB1_TARGETS_DN, GOBP_NUCLEUS_ORGANIZATION, GOBP_DETOXIFICATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_PROTEIN_FOLDING, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION

GO Biological Process (3): sperm DNA condensation (GO:0035092), ‘de novo’ post-translational protein folding (GO:0051084), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (4): thioredoxin peroxidase activity (GO:0008379), selenium binding (GO:0008430), oxidoreductase activity (GO:0016491), protein binding (GO:0005515)

GO Cellular Component (2): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	1
spermatid nucleus differentiation	1
‘de novo’ protein folding	1
cellular detoxification	1
thioredoxin-dependent peroxiredoxin activity	1
small molecule binding	1
catalytic activity	1
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOF	UGGT1	Q9NYU2	986
SELENOF	UGGT2	Q9NYU1	948
SELENOF	SELENOT	P62341	914
SELENOF	SELENOS	Q9BQE4	912
SELENOF	SELENOM	Q8WWX9	892
SELENOF	SELENOK	Q9Y6D0	892
SELENOF	SELENON	Q9NZV5	872
SELENOF	SELENOO	Q9BVL4	850
SELENOF	SELENOH	Q8IZQ5	841
SELENOF	SEPHS2	Q99611	828
SELENOF	SELENOI	Q9C0D9	814
SELENOF	SECISBP2	Q96T21	810
SELENOF	SELENOW	P63302	801
SELENOF	SELENOV	P59797	799
SELENOF	TXNRD3	Q86VQ6	795

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SELENOF	RDH11	psi-mi:“MI:0915”(physical association)	0.610
SELENOF	RDH11	psi-mi:“MI:2364”(proximity)	0.610
SELENOF	TUBB4A	psi-mi:“MI:0915”(physical association)	0.370
SELENOF	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.370
SELENOF	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
SELENOF	BAMBI	psi-mi:“MI:0915”(physical association)	0.370
XRCC6	SELENOF	psi-mi:“MI:0915”(physical association)	0.370
LGALS3BP	CEP290	psi-mi:“MI:0914”(association)	0.350
ORF47	ZZEF1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	CLGN	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350
	TOR1B	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
G	PGRMC2	psi-mi:“MI:0914”(association)	0.350
ERN2	SEC16A	psi-mi:“MI:0914”(association)	0.350
INSR	HAX1	psi-mi:“MI:0914”(association)	0.350
ANKRD46	NBAS	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
DNAJA1	HSPA8	psi-mi:“MI:0914”(association)	0.350
SEC61B	RPS3A	psi-mi:“MI:0914”(association)	0.350
SELENOF	SERPINB7	psi-mi:“MI:0914”(association)	0.350
IL25	POTEF	psi-mi:“MI:0914”(association)	0.350
HHIPL1	CYTH3	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): SEP15 (Proximity Label-MS), SEP15 (Proximity Label-MS), SEP15 (Affinity Capture-MS), SEP15 (Affinity Capture-MS), SEP15 (Affinity Capture-MS), SEP15 (Affinity Capture-MS), SEP15 (Affinity Capture-MS), SEP15 (Affinity Capture-MS), RDH11 (Two-hybrid), TUBB4A (Two-hybrid), SEPT3 (Two-hybrid), SEP15 (FRET), RDH11 (Affinity Capture-Western), SEP15 (Affinity Capture-Western), RDH11 (Reconstituted Complex)

ESM2 similar proteins: A1Z623, A2SXS5, A8YXY3, F1LQY6, O02718, O19011, O60613, P01137, P04202, P07200, P09533, P11456, P18341, P50747, P54831, Q08BI9, Q0P5I0, Q1LZ96, Q2KIJ6, Q2TBX5, Q38HS2, Q3UHE1, Q3UX43, Q58CS8, Q5C9Z4, Q5R812, Q5RB75, Q6IEE6, Q6PCX7, Q6X4M2, Q802F3, Q802G7, Q8BJQ9, Q8IVD9, Q8NC56, Q8R1N4, Q8R1T1, Q8TDX6, Q8VHC3, Q8WUX9

Diamond homologs: A1Z623, A8YXY3, O60613, Q6X4M2, Q802F3, Q923V8, Q9ERR7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SELENOF	“up-regulates activity”	UGGT2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ER-Phagosome pathway	5	19.1×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	5	12.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

40 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1208 predictions. Top by Δscore:

Variant	Effect	Δscore
1:86863602:CATA:C	acceptor_gain	1.0000
1:86863603:ATA:A	acceptor_gain	1.0000
1:86863604:TA:T	acceptor_gain	1.0000
1:86863605:ACT:A	acceptor_loss	1.0000
1:86863606:C:CA	acceptor_loss	1.0000
1:86863606:C:CC	acceptor_gain	1.0000
1:86880721:TACAG:T	acceptor_gain	1.0000
1:86880726:C:CC	acceptor_gain	1.0000
1:86903303:T:TA	donor_gain	1.0000
1:86908558:TGAC:T	donor_gain	1.0000
1:86863601:ACATA:A	acceptor_gain	0.9900
1:86863602:CATAC:C	acceptor_gain	0.9900
1:86868104:T:C	acceptor_gain	0.9900
1:86880722:ACAG:A	acceptor_gain	0.9900
1:86880722:ACAGC:A	acceptor_gain	0.9900
1:86880723:CAG:C	acceptor_gain	0.9900
1:86880723:CAGC:C	acceptor_gain	0.9900
1:86880723:CAGCT:C	acceptor_gain	0.9900
1:86880724:AG:A	acceptor_gain	0.9900
1:86880724:AGCT:A	acceptor_gain	0.9900
1:86880725:GCTA:G	acceptor_loss	0.9900
1:86880725:GCTAC:G	acceptor_gain	0.9900
1:86887197:C:CC	acceptor_gain	0.9900
1:86887204:T:TC	acceptor_gain	0.9900
1:86903275:CAGTA:C	donor_loss	0.9900
1:86903276:AGTAC:A	donor_loss	0.9900
1:86903278:TAC:T	donor_loss	0.9900
1:86903279:ACCT:A	donor_loss	0.9900
1:86903280:C:CG	donor_loss	0.9900
1:86903446:CAC:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006305 (1:86864287 T>C), RS1000037087 (1:86878201 A>C,T), RS1000067556 (1:86876185 A>G), RS1000098268 (1:86875910 T>C), RS1000229873 (1:86893965 A>G), RS1000306100 (1:86900661 G>A,C), RS1000321830 (1:86882164 G>A), RS1000408896 (1:86870049 A>C,G), RS1000424420 (1:86888552 G>A), RS1000530176 (1:86893081 A>G), RS1000585156 (1:86900839 G>A), RS1000600024 (1:86894296 A>C,G), RS1000608637 (1:86862406 T>A,C), RS1000643447 (1:86902086 A>C,G), RS1000687722 (1:86887520 A>G)

Disease associations

OMIM: gene MIM:606254 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases expression	2
chloropicrin	decreases expression, increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
selenomethylselenocysteine	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
zinc chromate	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, decreases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Potassium Dichromate	decreases expression	1
Selenium	decreases response to substance	1
Smoke	increases abundance, increases expression	1
Dronabinol	increases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.